Inflammation is a critical and natural biological response in an animal's body to help protect itself from infections, irritants or injuries. There are three types of inflammation that occur in animal systems: acute, chronic and systemic.
Acute inflammation is the body's immediate reaction to injury, be it physical, microbial or toxin related. Chronic inflammation generally involves a stronger reaction that calls on the immune system to fight particularly strong infections or diseases over an extended period. A complex biological cascade of molecular and cellular signals underlies the inflammatory process and the physiological responses.
When any harmful agent first enters the system, pro-inflammatory cytokines, which are the signalling proteins secreted by immune system cells, are released. This alerts the entire immune system to the presence of an unwanted and potentially harmful agent in the body. After an initial inflammation period, inflammation regulators are produced to reduce extended damage to healthy tissue.
Remediation is carried out by simultaneously destroying and healing the inflamed tissues until all affected tissues are gone. In a healthy biological process this serves to internally manage chronic inflammation challenges for a healthy outcome. In some cases, the animal's body can sacrifice some healthy tissue to limit the greater threat caused by the injury.
However, when the inflammatory system is compromised in some way, abnormalities in immune response can create a host of inflammatory disorders. Chronic inflammation becomes a concern when the cycle of inflammation and regulation becomes so extended that healthy tissues are affected, or so that the signals are no longer properly regulated. This can occur through genetic defect, when invasive organisms prove difficult to remove (such as in the case of multi-drug resistant organisms), through environmental influences (such as pro inflammatory diet factors) or as combinations of the above.
Systemic inflammation occurs when unchecked chronic inflammation reaches a critical stage and moves beyond local tissue and into the lining of blood vessels and organs. The specific management and response to this ongoing exposure is determined by complex factors such as genetics, diet, allergies, environmental factors, lifestyle and even mental health. It is the constant biological stress and immune system activity that will result in systemic pro-inflammatory states transitioning to secondary diseases and symptoms. Recently, it has been shown that two of the mechanisms that the body uses to regulate inflammation are dietary antioxidants and maintaining a balanced microbiome that inhibits the growth of pro-inflammatory bacteria. A diet low in essential micronutrients and antioxidants, such as a diet high in processed fat and starchy foods, has been found to promote the growth of pro-inflammatory bacteria. The consumption of such a diet on a regular basis will result in the frequent triggering of the inflammatory state. However, the body may lack the nutrition required to counter the pro-inflammatory signals.
The systemic inflammation response involves a large number of mediators, some of which are used as clinical or diagnostic markers of inflammation or inflammatory disease. One class of mediator bio-molecule that is linked to cell signalling and inflammatory responses is cytokines, a broad category of small proteins. Cytokine's physiological role in inflammatory processes and pathologic role in systemic inflammatory states have been increasingly recognised. Recently published studies on development of early stage type-2 diabetes in animal models describe an inflammatory link via macrophage invasion of pancreatic tissue, thus releasing large quantities of pro-inflammatory cytokines. It is reported that this cytokine response in pancreatic tissue damages the insulin producing beta cells leading to the onset of diabetic states through the immune cell activity.
A sub-class of proteins that play a key role in the innate immune system as well as the digestive system are Toll-like receptors (TLRs). Primarily their activation response is the release of the pro-inflammatory cytokines. The inflammatory response provoked by Toll Like-Receptor activation has led to the thought that endogenous activators of Toll Like-Receptors may hold a causal link to autoimmune disease development. Mounting evidence suggests several TLR sub-classes are involved in processes that impair insulin signaling in insulin-responsive organs. In fact, a distinctive feature of obesity is a low-grade level of inflammation, likely originating in the expanding adipose tissue.
The diagnostic tests available to clinicians to measure general levels of systemic inflammation include: C-reactive protein (CRP), Erythrocyte sedimentation rate (ESR), Extractable Nuclear Antigens (ENA), Antinuclear Antibodies (ANA), white blood cell count and albumin levels. All of these tests are non-specific as abnormal levels might result from a condition unrelated to inflammation. Various cytokines and adhesion molecules are not often used in a clinical setting primarily because they are not diagnostic in identifying a source of inflammation in the body.
A number of chronic diseases have inflammatory components, such as Auto-immune diseases, diabetes, gestational diabetes, asthma, diverticulitis, rheumatoid arthritis, atherosclerosis, IBS, chronic fatigue syndrome, psoriasis, IBD, and cancer. Current research has indicated preliminary inflammatory and intestinal health components to Alzheimer's disease, autism, depression and a range of mental disorders, and menopause. The underlying causal mechanism of these diseases is unknown and the role of inflammation in disease pathogenesis is under significant scientific and medical investigation.
Dietary intake is recognised as one of the main mitigating factors of systemic inflammation and has been reported to modulate inflammatory responses within the body. Overall, studies suggest that diets rich in high Glycemic Index (GI) foods (simple sugars and carbohydrates), trans-fats (hydrogenated or partially hydrogenated oils) and saturated fats, tend to stimulate inflammation.
In contrast, a diet rich in monounsaturated fatty acids from olive oil, fruits and vegetables, nuts, beans, and whole plant grains has been shown to reduce inflammation. Studies investigating links between dietary fibre, low GI foods and inflammatory responses are further revealing the bi-directional relationship between the host immune system and gut micro-flora. It has been reported that dietary fibre supplementation may provide a strategy for manipulating the intestinal bacterial profile, changing the interaction with the mucosal immune system, thereby modulating the host immune system.
Essential fatty acids play a role in the body's inflammatory processes. Increasing the dietary intake of omega-3 fatty acids (eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)) found in oily fish and fish oils, as well as some marine plants, generally decreases Inflammatory markers (IM) whereas an increase in the dietary intake of omega-6 fatty acids has been observed to increase IM's. The specific ratio of omega-6 to omega-3 fatty acids has been researched with a typical western diet consisting of approximately 16:1 Omega-6 to Omega-3. However it is estimated that humans evolved with an omega fat ratio closer to 1:1 and this may be a worthwhile dietary target to reduce inflammatory responses in the body.
Current research links phytochemicals, polyphenolic compounds, catechins, specific vitamins and minerals to the therapeutic reduction of inflammation associated diseases. Some reports links natural spices and herbs to direct inhibition of pro-inflammatory pathways. Traditionally, herbs and spices have been used to increase antioxidant and micronutrient quantity in a diet.
The mechanisms of all these nutritional effects, both positive and negative, are now being primarily focused in the gut health of the host. Gut health will refer to the normal function, shape, size and permeability of tissues in the stomach, small intestine (Duodenum, Jejunum, Ileum), large intestine (Caecum, colon, Rectum). Each of these regions of the gastrointestinal tract has mucosal and sub-mucosal linings that govern nutrient passage. Along the entire tract resides the largest collections of foreign cells in the human body, both in variety and total numbers. These microbial populations are referred to as the microbiome or ‘the ecological community of commensal, symbiotic, and pathogenic microorganisms that literally share our body space’.
Studies now link Type-I diabetes as an autoimmune disease that is correlated with a multiplicity of predisposing factors, including aberrant intestinal microbiome, a permeable intestinal mucosal barrier, and intrinsic differences in immune responsiveness. It has been stated by proponents in the medical community that up to 70% of the immune system is underneath the bowel lining, and that the immune system is significantly affected when partially digested food particles can pass through the bowel wall. Additionally, mouse studies are indicating links between a dysfunctional microbiome and diabetes, gastrointestinal diseases, asthma, allergy and obesity. The interaction of the microbiome with the immune system, as mediated by the gut, likely plays a vital role in the development and treatment of many inflammatory and autoimmune diseases.
Nutritional intake is becoming more recognised as a corrective action to restore a dysfunctional microbiome to normality. Nutritional treatments are recognised not only as a preventative to inflammatory conditions an effective alternative to pharmaceutical drugs without the adverse side effects of many pharmaceuticals.
As an example of a causal link to dietary intake in auto-immune conditions, it is becoming accepted that gestational diabetes has a significant relationship to nutrition, and it has been suggested that many cases of gestational diabetes may be treated with nutritional supplements or a targeted nutritional diet.
People who suffer from all types of diabetes mellitus, (Type I, II & LADA-Latent Auto-Immune Diabetes in Adults) have been found to have a higher incidence of other chronic conditions than the general population including inflammation caused by oxidative stress and gastro-intestinal disorders. This means that the presence of potential food allergies and/or malabsorption can play a major role in the selection of diet control for diabetic individuals. Common food allergies and intolerances of diabetes sufferers have been reported with respect to wheat, dairy, soy, and oats (amongst others). It has been estimated that 2% of the general population suffers from food allergies however diabetics are reported to have increased risk of developing food allergies and intolerances. Large scale cohort studies of multiple ethnicities and lifestyles have shown that regardless of other factors (such as genetic predisposition and body weight) a “healthy” diet has a statistically significant improvement on outcomes both for diabetes mellitus itself and secondary correlating diseases.
The proportion of individuals suffering an autoimmune & inflammation related conditions is clearly on the rise, with an associated correlation to the modern western diet. Emerging research suggests that digestive abnormalities may be the underlying cause of degenerative gut health and many auto-immune diseases.
Accordingly, it is an object of the invention to introduce a food ingredient to the diet of individuals that are at risk or suffering chronic systemic inflammatory and auto-immune conditions initiated, or adversely affected, by poor digestive health, that assists in ameliorating the underlying inflammatory mechanism and reducing symptoms.